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Oscar F. Lopez Nunez, Jacqueline A. Rymer, and Kenichi Tamama. Case of Sudden Acute Coma Followed by Spontaneous Recovery. J Appl Lab Med 2018;3:506-10.

Guest

Dr. Kenichi Tamama is Associate Professor of Pathology and Medical Director of Clinical Toxicology Laboratory at the University of Pittsburgh Medical Center. Dr. Oscar Lopez Nunez is an Anatomic and Clinical Pathology Resident at the University of Pittsburgh Medical Center.

Transcript

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Randye Kaye:
Hello, and welcome to this edition of “JALM Talk” from The Journal of Applied Laboratory Medicine, a publication of the American Association for Clinical Chemistry. I’m your host, Randye Kaye.

Clinical laboratories play a crucial role in emergency medicine through toxicology and drug testing. The type of testing provided is often a balance between laboratory resources and the patient population served. Each approach to drug screening comes with advantages and disadvantages depending upon the specific drug exposure or illicit drug suspected. A “Case of Sudden Acute Coma Followed by Spontaneous Recovery” was published in the November 2018 issue of The Journal of Applied Laboratory Medicine. The Case Study details the presentation and resolution for an unresponsive patient admitted to the hospital with a history of drug and alcohol abuse with a negative urine drug screen.

The corresponding author is Dr. Kenichi Tamama. Dr. Tamama is Associate Professor of Pathology and Medical Director of Clinical Toxicology Laboratory at the University of Pittsburgh Medical Center. He is joined by Dr. Oscar Lopez Nunez, an Anatomic and Clinical Pathology Resident at the University of Pittsburgh Medical Center (UPMC), who is currently completing his fellowship training in Pediatric Pathology at the UPMC Children’s Hospital of Pittsburgh. Welcome Dr. Tamama and Dr. Lopez Nunez. Here’s my first question, can you just tell me a little bit about what made the case interesting, and the presentation of the patient?

Kenichi Tamama:
I think the interesting point of this case is that we, the laboratorians, are in the driver’s seat to make the diagnosis which was totally unexpected by the clinical team. In other words, this case highlights the importance of the laboratory and laboratory medicine in the patient’s care.

Randye Kaye:
And that’s a very good thing, excellent. So, now the patient reported in your case was found to have 1,4-Butanediol, 1,4 BD, in his urine after a comprehensive urine drug screen was performed. What exactly is 1,4 BD and why is this important?

Kenichi Tamama:
The 1,4-Butanediol, or 1,4 BD, is a prodrug of GHB or gamma-hydroxybutyrate. The identification of 1,4 Butanediol in the patient’s urine specimen indicates possible GHB abuse and so we discussed the lab findings with the clinical team at that time and actually, the patient was admitted as a questionable opioid overdose case and GHB overdose was not among their differential list. But the patient did not respond to naloxone, which is not consistent with the opioid overdose, and that they agreed that the GHB overdose fit the overall picture better than opioid overdose.

Randye Kaye:
I see. Okay, so can you tell me more about, what is GHB? Tell me more.

Oscar Lopez Nunez:
Sure. GHB stands for gamma-hydroxybutyrate. This is a short chain carboxylic acid that works as a precursor as well as degradation product of the inhibitory neurotransmitter GABA in the brain. Additionally, GHB works as a neurotransmitter after binding to its own receptor and although its function is largely unknown, we do know it is able to stimulate the release of growth hormone. That is why it was included in the body builders’ formula back in the ‘90s when it was not regulated.

Now, as GABA-mimetic, GHB and its prodrugs, gammabutyrolactone and 1,4-Butanediol, has been abused since ‘90s among body builders and others. These compounds are highly addictive, secondary to the rebound insomnia and anxiety they produce when not in use. The recreational use of GHB has been reported in the setting of rave parties, changes euphoria, relaxation, and sedation. The odorless and colorless of GHB as well as its profound CNS suppressive symptoms make it a date-rape substance that is currently considered a schedule one drug by the DEA.

Randye Kaye:
Wow, so what are the hallmark signs and the symptoms of a GHB intoxication?

Oscar Lopez Nunez:
Well, the clinical hallmark of GHB overdose is the rapid onset of profound coma as well as myoclonus, respiratory depression, hypoventilation, and bradycardia. These signs persist for an unusual short period of time given the depth of the coma.

Of note, the GHB is typically combined with alcohol, which potentiates its respiratory depression and sedative effect increasing the risks of death. Besides the respiratory compromise, users can also die due to aspiration, pulmonary edema, trauma, or even potential asphyxia due to the sudden loss of consciousness in the setting of a GHB overdose.

Randye Kaye:
So, why was the rapid urine screening not able to detect these compounds in the urine? What’s the role of a comprehensive drug screening? How does it differ from the confirmatory test that ultimately was done?

Kenichi Tamama:
The rapid urine drug screening panel is a standard immune based assay and such, it has shortcomings as we target specific and predefined substances only. Neither GHB or any of its precursors are included in this panel and that is why these substances were missed on admission.

The comprehensive drug screening, or what we call CDS, is a GC-MS based untargeted drug screening that provides a more comprehensive coverage outside the rapid urine screening panel. In this case, the CDS, comprehensive drug screening, identified a large peak of a mass spectrum consistent with 1, 4-Butanediol.

This finally prompted a more specific confirmatory test that documented the presence of both compounds, that is GHB and 1,4-Butanediol, in the remaining urine specimen. Both CDS and the GHB confirmatory tests are GC-MS based procedures. However, the confirmatory test also involves derivatization of the samples enabling GHB detection in a targeted manner.

Randye Kaye:
Very, very interesting case and an important one. Thank you so much for joining us today, doctors.

Kenichi Tamama:
Thank you very much for having us.

Randye Kaye:
That was Dr. Kenichi Tamama and Dr. Oscar Lopez Nunez from the University of Pittsburgh’s School of Medicine talking about a “Case of Sudden Acute Coma Followed by Spontaneous Recovery” from the November 2018 Issue of JALM. Thanks for tuning in to this episode of “JALM Talk” See you next time and don’t forget to submit something for us to talk about.